title: Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation.
abstract: OBJECTIVE
  Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment.
  
  
  RESULTS
  Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than one ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation.
  
  
  METHODS
  Data provide evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition.
  
  
  CONCLUSIONS
  Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggest that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing long-term neurocognitive sequelae.
authors.affiliation: 1 Department of Internal Medicine, Duke University Medical Center , Durham, North Carolina.
authors.forename: Bertrand P
authors.initials: BP
authors.lastname: Tseng
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.forename: Atefeh
authors.initials: A
authors.lastname: Izadi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Suarez
authors.forename: Mary L
authors.initials: ML
authors.lastname: Lan
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Tran
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects*; D011839:Radiation, Ionizing; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species